Trial Information

A Phase II Study of VEGF-Trap in Recurrent or Metastatic Gynecologic Soft-Tissue Sarcomas

PRIMARY OBJECTIVES:

I. To assess the objective response of recurrent or metastatic gynecologic soft-tissue
sarcomas to VEGF-Trap (ziv-aflibercept).

II. To assess the incidence of disease stabilization, as measured by 6-month
progression-free survival, in patients with recurrent or metastatic gynecologic soft-tissue
sarcomas treated with VEGF-Trap.

SECONDARY OBJECTIVES:

I. To assess time-to-progression and overall survival in patients with recurrent or
metastatic gynecologic soft-tissue sarcoma treated with VEGF-Trap.

* As of 24 October 2012, overall survival follow-up is to be discontinued for the one
remaining patient on long term follow-up, who has been off protocol therapy for at least 3
years. Time to progression and median survival times have been based on the currently
available data.

II. To assess the toxicity associated with VEGF-Trap in patients with recurrent or
metastatic gynecologic soft-tissue sarcoma.

III. To characterize the population pharmacokinetics of VEGF-Trap and to explore for
demographic and clinical covariates

OUTLINE: This is an open-label, multicenter study.

Patients are stratified according to histology (uterine leiomyosarcoma vs malignant mixed
mullerian tumor/carcinosarcoma). Patients receive ziv-aflibercept over 1 hour on day 1.
Treatment repeats every 14 days in the absence of disease progression or unacceptable
toxicity. Patients undergo blood collection at baseline, every 8 weeks during treatment, and
60 days after completion of study treatment for population pharmacokinetic analysis using
enzyme-linked immunosorbent assay (ELISA).

After completion of study treatment, patients are followed at 4 weeks and then every 3
months thereafter.

Inclusion Criteria:

- Histologically or cytologically confirmed soft tissue sarcoma of the gynecologic
tract, including 1 of the following subtypes: uterine leiomyosarcoma, malignant mixed
mullerian tumor/carcinosarcoma, disease originating in the ovary or fallopian tube
allowed

- Locally advanced, unresectable, or metastatic disease

- Previously treated disease must have radiographic or clinical evidence of progressive
disease

- Patients must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded) as >=
20 mm with conventional techniques or as >= 10 mm with spiral CT scan

- Indicator lesions may not have been previously treated with surgery, radiotherapy, or
radiofrequency ablation unless progressive disease has been confirmed

- No evidence of CNS disease, including primary brain tumor or brain metastasis

- OR; Antihypertensive medications allowed, as long as the dose and number of
antihypertensive medications have not been increased within the past 2 weeks,
Myocardial infarction, coronary artery bypass graft, or unstable angina within the
past 6 months, OR;

- Concurrent full-dose anticoagulants (e.g., warfarin) with INR > 1.5 allowed provided
all the following criteria are met:, In-range INR (usually between 2-3) on a stable
dose of oral anticoagulant or on a stable dose of low molecular weight heparin,

- OR; For patients on warfarin, the upper target for INR is ≤ 3 No active bleeding or
pathological condition that carries a high risk of bleeding (e.g., tumor invading
major vessels or known varices)

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